The stomach is an organ of digestion. It has a saclike shape and is located between the esophagus and the intestines. Almost every animal has a stomach.
The human stomach is a muscular, elastic, pear-shaped bag, lying crosswise in the abdominal cavity beneath the diaphragm. It changes size and shape according to its position within the body and the amount of food inside. The wall of the stomach is lined with millions of gastric glands, which together secrete 400-800 ml of gastric juice at each meal. Three kinds of cells are found in the gastric glands. These cells are parietal cells, “chief” cells and mucus-secreting cells. Parietal cells contain an enzyme known as H+/K+ adenosine triphosphatase. H+/K+ adenosine triphosphatase is also referred to as an “acid pump” or “proton pump”. This transmembrane protein secretes H+ ions (protons) by active transport, using the energy of ATP. The concentration of H+ in the gastric juice can be as high as 0.15 M, giving gastric juice a pH less than 1.
Proton pump inhibitors (or “PPIs”) are a class of pharmaceutical compounds that inhibit gastric acid secretions by inhibiting H+/K+ adenosine triphosphatase. It is known in the art that proton pumps can exist in either an active state or a dormant state. PPIs only bind to the active proton pumps. PPIs are metabolized in the parietal cells to active sulfenamide metabolites that inactivate the sulfhydryl group of the proton pump, thereby reducing the hydrogen ion secretion (Langtry and Wilde, “An update of its pharmacological properties and clinical efficacy in the management of acid-related disorders,” Drugs, 54(3): 473-500 (1997)).
PPIs are frequently prescribed for short-term treatment of active duodenal ulcers, gastric ulcers, gastroesophageal reflux disease (GERD), severe erosive esophagitis, poorly responsive systematic GERD, and pathological hypersecretory conditions such as Zollinger Ellison syndrome. These conditions are caused by an imbalance between acid and pepsin production (aggressive factors), and mucous, bicarbonate and prostaglandin production (defensive factors). The above listed conditions can arise in healthy or critically ill patients, and may be accompanied by significant gastrointestinal bleeding.
Lansoprazole, a PPI, sold commercially under the brand name PREVACID®, is a substituted benzimidazole, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]benzimidazole. Lansoprazole is a racemic compound, containing a R-enantiomer and a S-enantiomer. The R-enantiomer of lansoprazole, also known as dexlansoprazole, is also a PPI (See, WO 2004/035020).
PPIs are dosed to patients in need of treatment thereof in conjunction with the intake or consumption of food or a meal. For example, the labeling for PREVACID® (lansoprazole) states that PREVACID® “should be taken before eating” and the labeling for NEXIUM® (esomeprazole magnesium), also a PPI, states that “NEXIUM® should be taken at least one hour before meals.” Therefore, patients are unable to take PPIs whenever it is convenient for them to do so, but instead must remember to take their medication with the intake or consumption of food or at least one hour before the intake or consumption of food. In order to improve patience compliance, there is a need in the art for pharmaceutical compositions containing PPIs, such as dexlansoprazole, that can be dosed to a patient independently of the intake or consumption of food.